Atrophy in Thalamus Can Predict Multiple Sclerosis

These measurements offer an improvement over current methods for evaluating patients at risk for MS.

MS develops as the body’s immune system attacks and damages myelin, the protective layer of fatty tissue that surrounds nerve cells within the brain and spinal cord. Symptoms include visual disturbances, muscle weakness, and trouble with coordination and balance. People with severe cases can lose the ability to speak or walk. About 85% of people with MS undergo a first, short-term neurologic episode known as clinically isolated syndrome (CIS). A definitive MS diagnosis is based on a combination of factors, including neurologic exams, medical history, development of a second clinical event, and detection of new and broadening lesions with contrast-enhanced or T2-weighted MRI.

The study’s findings were published online April 23, 2013, in the journal Radiology. “For some time we’ve been trying to understand MRI biomarkers that predict MS development from the first onset of the disease,” said Robert Zivadinov, MD, PhD, FAAN, from the Buffalo Neuroimaging Analysis Center of the University at Buffalo (NY, USA). “In the last couple of years, research has become much more focused on the thalamus.”

Recent studies found atrophy of the thalamus in all different MS disease types and detected thalamic volume loss in pediatric MS patients. “Thalamic atrophy may become a hallmark of how we look at the disease and how we develop drugs to treat it,” Dr. Zivadinov said.

Dr. Zivadinov and colleagues, for the study, examined the association between the development of thalamic atrophy and conversion to clinically confirmed MS. “One of the most important reasons for the study was to understand which regions of the brain are most predictive of a second clinical attack,” he said. “No one has really looked at this over the long term in a clinical trial.”

The researchers used contrast-enhanced MRI for initial assessment of 216 CIS patients. They performed follow-up scans at six months, one year, and two years. Over two years, 92 of 216 patients, or 42.6%, converted to clinically definite MS. Decreases in thalamic volume and increase in lateral ventricle volumes were the only MRI measures independently linked with the development of clinically definite MS. “First, these results show that atrophy of the thalamus is associated with MS,” Dr. Zivadinov said. “Second, they show that thalamic atrophy is a better predictor of clinically definite MS than accumulation of T2-weighted and contrast-enhanced lesions.”

The findings suggest that measurement of thalamic atrophy and increase in ventricular size may help identify patients at high risk for conversion to clinically definite MS in future clinical trials involving CIS patients. “Thalamic atrophy is an ideal MRI biomarker because it’s detectable at very early stage,” Dr. Zivadinov said. “It has very good predictive value, and you will see it used more and more in the future.”

The researchers continue to monitor the study group, with plans to publish findings from the four-year follow-up in 2015. They are also trying to determine more about the physiology of the thalamic involvement in MS. “The next step is to look at where the lesions develop over two years with respect to the location of the atrophy,” Dr. Zivadinov said. “Thalamic atrophy cannot be explained entirely by accumulation of lesions; there must be an independent component that leads to loss of thalamus.”

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